Recombinant protein c variants

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 9/64 (2006.01) A61K 38/36 (2006.01) A61P 7/02 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2477876

The present invention is concerned with a variant blood coagulation component, which is substantially homologous in amino acid sequence to a wild-type blood coagulation component capable of exhibiting anticoagulant activity in the protein C-anticoagulant system of blood and selected from protein C (PC) and activated protein C (APC), said variant component being capable of exhibiting an anticoagulant activity, that is enhanced in comparison with the anticoagulant activity expressed by the corresponding wild-type blood coagulation component, and said variant component differing from the respective wild-type component, in that it contains in comparison with said wild-type component at least one amino acid residue modification in its N- terminal amino acid residue sequence that constitutes the Gla-domain of protein C and at least one amino acid residue modification in the serine- protease domain of protein C. The present invention is also concerned with methods to produce such variants based on DNA technology; with DNA segments intended for use in the said methods; and with use of said variants for therapeutic and diagnostic purposes.

La présente invention concerne un constituant variant de coagulation sanguine, lequel est sensiblement homologue, en séquence d'acides aminés, à un constituant de coagulation sanguine de type sauvage capable de présenter une activité anticoagulante dans le système anticoagulant à protéine C du sang et sélectionné entre la protéine C (PC) et la protéine C activée (APC), ledit constituant variant étant capable de présenter une activité anticoagulante, laquelle est améliorée en comparaison avec l'activité anticoagulante exprimée par le constituant de coagulation sanguine de type sauvage correspondant, et ledit constituant variant différant du constituant de type sauvage respectif en ce qu'il contient, comparé audit constituant de type sauvage, au moins une modification de reste d'acide aminé dans sa séquence de restes d'acides aminés N-terminale qui constitue le domaine Gla de la protéine C, et au moins une modification de reste d'acide aminé dans le domaine sérine-protéase de la protéine C. La présente invention concerne également des procédés de production de ces variants basés sur le génie génétique, avec des segments d'ADN destinés à être utilisés dans lesdits procédés, et par l'utilisation desdits variants à des fins thérapeutiques et diagnostiques.

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